2006
DOI: 10.1097/00002826-200603000-00001
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Impact of Gastric Emptying on Levodopa Pharmacokinetics in Parkinson Disease Patients

Abstract: Adjunction of the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) to levodopa/carbidopa (LD/CD) improves motor symptoms in patients with Parkinson disease (PD) by a prolonged elimination of LD. But it is not known whether EN addition influences gastric emptying and thus LD pharmacokinetics and pharmacodynamics. Objectives were to simultaneously determine plasma LD elimination, gastric emptying, and clinical response after a single intake of the same LD dosage as LD/CD--or as (LD/CD/EN) formulatio… Show more

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Cited by 123 publications
(73 citation statements)
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“…In contrast, the pharmacokinetics of oral L-dopa largely depends on various factors, such as gastric emptying, which is known to be slow in MSA patients (11). This results in considerable variability among patients (12). Furthermore, the plasma half-life is also different between L-dopa and pramipexole.…”
Section: Discussionmentioning
confidence: 99%
“…In contrast, the pharmacokinetics of oral L-dopa largely depends on various factors, such as gastric emptying, which is known to be slow in MSA patients (11). This results in considerable variability among patients (12). Furthermore, the plasma half-life is also different between L-dopa and pramipexole.…”
Section: Discussionmentioning
confidence: 99%
“…The GE has been shown to be delayed in PD patients (25)(26)(27)(28)(29)(30) resulting in an impaired bioavailability of levodopa (31)(32)(33)(34). Another factor is the competition between levodopa and other large neutral amino acids (LNAAs) that share the same active transport carrier system across the intestinal mucosa in the small intestine and a high amount of dietary proteins has been proposed to decrease the levodopa uptake (35)(36)(37).…”
Section: Levodopa In the Peripherymentioning
confidence: 99%
“…Orally given levodopa is absorbed in the proximal one-third of the small intestine and, except for the competition between levodopa and other LNAAs across the intestinal mucosa (35,36), GE is an important factor (24). It has been shown that more than 70 % of PD patients suffer from impaired gastric motility (27,31) with symptoms like early satiety, postprandial bloating and nausea and it has been suggested that this is caused by the delay in GE that has been shown in PD patients (25)(26)(27)(28)(29)(30)(136)(137)(138). Delayed GE has also been shown to impair the levodopa uptake and is therefore suggested to worsen motor complications (31)(32)(33)(34)136).…”
Section: Gastric Emptyingmentioning
confidence: 99%
“…18 Several studies have demonstrated a significant relationship between gastric emptying and L-dopa pharmacokinetics in PD patients, suggesting that delayed gastric emptying contributes to delayed ON and other motor fluctuations. [22][23][24] Other drugs, including dopamine agonists, anticholinergics, amantadine, inhibitors of monoamine oxidase and catechol-O-methyltransferase (COMT), may also contribute to GId. 25 L-dopa can increase gastric acid secretion, impair gastric relaxation, and delay gastric emptying; 14,26,27 anticholinergics and amantadine commonly cause dry mouth and constipation; and COMT inhibitors can cause diarrhoea.…”
Section: The Emerging Role Of Nonmotor Aspectsmentioning
confidence: 99%